The objective of this proposal is to gain further insight into the antithrombotic action of heparin so as to improve the efficiency of this drug in the prevention of thromboembolic disease. We have recently developed two assays - one measures quantitatively the amount of antithrombin III in plasma, the other determines the rate at which antithrombin III reacts with activated clotting factor X (Xa). These assays have provided a means of determining hypercoagulability before thrombin has altered the fibrinogen molecule. Since the determination of the presence or absence of thrombosis in man is often difficult, we propose to use an animal model for thrombosis that permits the comparative examination of in vitro and in vivo relationships as chemical reactions and modifications in heparin are induced to define the antithrombotic potential of this drug. Ability to recognize the initiation or prevention of thrombosis in animals also permits an integrated study of the relation between clot incitors and clot inhibitors.